14-94306092-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001756.4(SERPINA6):c.1011C>T(p.Asp337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,700 control chromosomes in the GnomAD database, including 17,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3233 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14430 hom.)
• Consequence: SERPINA6 NM_001756.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.21

Genes affected

SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-94306092-G-A is Benign according to our data. Variant chr14-94306092-G-A is described in ClinVar as [Benign]. Clinvar id is 3056658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA6	NM_001756.4	c.1011C>T	p.Asp337=	synonymous_variant	4/5	ENST00000341584.4
SERPINA6	XM_047431827.1	c.1182C>T	p.Asp394=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA6	ENST00000341584.4	c.1011C>T	p.Asp337=	synonymous_variant	4/5	1	NM_001756.4	P1
SERPINA6	ENST00000555056.1	c.*323C>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27633 AN: 152014 Hom.: 3220 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.130 AC: 32716 AN: 251364 Hom.: 2712 AF XY: 0.127 AC XY: 17215 AN XY: 135848

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.0911

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.00500

Gnomad SAS exome AF: 0.0887

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.133 AC: 194159 AN: 1461568 Hom.: 14430 Cov.: 34 AF XY: 0.131 AC XY: 95232 AN XY: 727120

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.0975

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.00562

Gnomad4 SAS exome AF: 0.0902

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.182 AC: 27678 AN: 152132 Hom.: 3233 Cov.: 32 AF XY: 0.177 AC XY: 13126 AN XY: 74366

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.191

Alfa AF: 0.154 Hom.: 1754

Bravo AF: 0.191

Asia WGS AF: 0.0750 AC: 260 AN: 3478

EpiCase AF: 0.150

EpiControl AF: 0.143

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SERPINA6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 07, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.9
Dann	Benign	0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2228543; hg19: chr14-94772429; COSMIC: COSV58587960;